By Jessica Lau
As stem cell researchers are making strides toward safe, effective therapies for patients, clinics around the world are selling unproven treatments that can cause lasting harm — such as patients developing blindness after receiving cell injections in the eye. To address the impact of such unproven treatments and lay out a path for how to bring stem cell therapies to patients responsibly, the Center for Bioethics at Harvard Medical School (HMS) hosted a discussion on September 5 with clinician-scientist and HMS dean George Q. Daley, M.D., Ph.D. and bioethicist Insoo Hyun, Ph.D.
Unproven stem cell treatments
In the U.S. alone, over 600 clinics sell unproven stem cell treatments. The treatments typically involve taking stem cells from one part of the patient’s body and injecting them into another part that is experiencing pain or disease.
“Patients say, what’s the problem? They’re my own cells, they’re in my own body — how could they hurt me?” said Hyun, who is a faculty member of the Center for Bioethics. “Well, cancer cells are also your own cells. And there are some cells you probably don’t want to put in other places in your body where you normally don’t find them — you don’t want bone cells in your brain, or in your eye.”
Different types of stem cells have different capacities to regenerate tissues. Stem cells in the developing embryo have the potential to become many types of cells, but adult stem cells are more limited in what they can become.
“When clinics offer a single cell therapy for multiple diseases, we just know that stem cells don’t have the versatility to address each of those issues,” said Daley, a principal faculty member of the Harvard Stem Cell Institute.
The importance of regulating cell therapies
Although the U.S. Food and Drug Administration (FDA) regulates medicines, clinics selling unproven treatments have exploited a loophole to avoid the government’s evaluation processes.
“The FDA does not govern and regulate medical practice or service. If you can argue that you’re simply taking that patient’s own stem cells from their body and put[ting] them back into their body within 48 hours, without expanding the cells or manipulating them, that counts as a medical bedside service and FDA is supposed to be hands off on that,” Hyun said.
In fact, cells have complicated biology that requires special consideration from a regulatory perspective. When dealing with conventional medicines like aspirin, the drug is a “small molecule” with straightforward properties. Researchers can readily analyze the drug to make sure it is manufactured correctly.
“Cells are a completely different animal,” Daley said. “What does it mean to have an identity of a cell, when a cell population typically involves a tremendous degree of heterogeneity? And cells, given their existence in culture, create additional problems for contamination.”
When a small molecule drug is tested in patients during a clinical trial, researchers measure how it gets processed by the body. Doing the same for cell therapies is more challenging.
“We lack tools for tracing the fate of cells as they find their way into their niche. If the stem cell actually engrafts and exists forever in the patient, the persistence of that is clearly different from the transient nature of a small molecule — just imagine how long one would actually have to evaluate a subject,” Daley said. “Cells are very different and they require a whole new set of principles when we think about manufacturing, their identity, and their evaluation in clinical trials.”
Balancing clinical trials and medical innovation
A clinical trial is the formal process of testing a new therapy in a group of patients, often including a comparison treatment to determine whether the new one has any effect. In addition to clinical trials, medicine also evolves through physicians helping individual patients.
“A tremendous amount of innovation, especially in the surgical sphere, has occurred through the process of trying to serve the medical needs of individuals. A surgeon has a patient on the operating table and they find an unusual anatomic situation — they have to innovate their way out of it,” Daley said.
To establish best practices for how medical innovation can be applied to stem cell therapies, Daley and Hyun worked with the International Society for Stem Cell Research (ISSCR). The guidelines they helped produce “allow the prospective physician to act in the best interest of their patients, as long as they were relatively few and seriously ill patients for whom there may be no alternative,” Daley said.
According to the guidelines, the physician should develop a plan that explains the scientific rationale for the treatment, the quality control that will be applied to the cells, and the accountability for any unexpected medical issues. All of this should be reviewed by independent experts and made clear to the patient.
“If you’re going to do an unproven intervention on patients, you should inform the patient and make sure the patient understands that this is an unproven intervention. In no case should an innovative medical therapy of this kind involve a responsibility for the patient to pay a significant, heavy price,” Daley said.
If the innovation leads to improvement in the patient’s outcome, then the physician has a responsibility to quickly bring it to a clinical trial process. That way, the treatment benefit can reach more patients.
“If you apply these criteria, most of the clinics that are involved in stem cell tourism will fall quite short,” Daley said. “When I hear from stem cell practitioners who are peddling unproven therapies and charging money for it, when I hear from them that they know it works and they’ve seen it work, I say prove it — prove it so that the rest of us can also benefit.”
Supporting the patient
The rise of unproven stem cell treatments has been attributed to a lack of government regulation and information for patients. But Hyun emphasized an additional factor: the patient’s disease experience.
Severe illness can cut patients off from how they find connection and meaning in life. This type of distress leads them to take actions, such as going to a stem cell clinic, to try to improve the situation. As physicians caution against unproven stem cell treatments, they also need to provide alternatives for patients.
“Besides the lack of regulation and lack of patient information, these are families in crisis,” Hyun said. “When families are in crisis, they don’t need more info — they need support.”